Lithium

Author: Stewart Shiu, Fifth Year Medical Student, University of Auckland, New Zealand, May 2016.

What is lithium?

Lithium is a chemical element and the lightest of the alkali metals. As it is highly reactive and flammable, it exists in nature in compounds. Lithium salts are used therapeutically in the treatment of mood disorders such as bipolar disorder and depression.

In New Zealand, lithium carbonate (a lithium salt) is fully subsidised and can be prescribed as 250 mg capsules, 250 mg or 400 mg tablets or 400 mg modified release tablets. Trade names include Lithicarb FC and Priadel. It is best taken with food to prevent nausea.

What is lithium used for?

Lithium is indicated for:

Prevention and treatment of mania, hypomania and depression in bipolar disorder

Prevention and treatment of recurrent unipolar depression

Combination therapy with other antidepressants for treatment resistant depression

Lithium has been used for over 60 years and is a mainstay in both prevention and acute treatment of bipolar disorder. Many placebo-controlled trials have shown its efficacy in reducing the frequency and severity of both the manic and depressive phases of bipolar disorder. It has also been shown to reduce the risk of suicide and death compared to placebo.

How long does it take for lithium to work?

If used for acute mania and hypomania, patients will experience a therapeutic effect within 6–10 days. When used for depression, there is a 6–8 week delay in its effect. Used for prevention, it can take 6–12 months before the full therapeutic effect is achieved.

What are the adverse effects of lithium?

Lithium has a narrow therapeutic index, which means there is a small difference between doses that are effective for treatment, and doses that are toxic. Because of this, regular blood tests are needed to check serum lithium levels. As lithium is excreted from the body through the kidneys, caution is required in patients with renal failure, as they are more likely to suffer from lithium accumulation and toxicity.

The adverse effects of lithium are usually dose-dependent and occur when serum lithium levels are above therapeutic levels.

Gastrointestinal side effects of lithium

Nausea, vomiting, anorexia and diarrhoea are more common in the initial stages of lithium therapy, when serum lithium levels are not yet stable.

Neurological side effects of lithium

At therapeutic levels, lithium can cause a persistent fine hand tremor, muscle weakness and rarely, extrapyramidal features. Tremors may be treated with a beta-blocker. Patients with lithium toxicity may have impaired consciousness, apathy, hyper-reflexia, hypertonia, seizures and rarely, death. Prolonged toxic exposure can lead to brain damage.

Endocrine side effects of lithium

Long-term lithium treatment can result in hypothyroidism and euthyroid goitre, especially in middle aged women. This responds well to treatment with supplementary thyroxine. Hypercalcaemia is reported in 10% of patients. Hypermagnesaemia and hyperparathyroidism have also been noted.

Renal side effects of lithium

Up to one-third of patients can develop nephrogenic diabetes insipidus, which presents as polyuria and polydipsia. This is reversible on discontinuation of lithium. Long-term treatment on lithium can cause irreversible impairment of renal function.

Cardiac side effects of lithium

Lithium can cause ECG changes and arrhythmias due to QT prolongation­. A recent myocardial infarction is a contraindication to lithium use.

Cutaneous adverse effects of lithium

The skin is the organ most commonly adversely affected by lithium.

Men are more likely to be affected.

Lithium has a higher rate of causing skin adverse effects compared to other psychotropic drugs used for mood disorders.

Compared to other organ systems, adverse effects of the skin occur even if serum lithium is still in the normal therapeutic range.

It can cause the first presentation of a skin disease or can exacerbate an existing disease, such as psoriasis or acne.

Not all patients with existing skin disease will flare up while on lithium.

Exacerbations of pre-existing skin disease may become resistant to usual treatment. The skin condition is reversible if lithium is stopped, except in some cases of psoriasis. Some conditions such as folliculitis resolve, even whilst continuing lithium treatment.

Lithium is contraindicated if taking another medication that causes QT prolongation, such as domperidone, hydroxyzine, mizolastine, piperaquine and sibutramine.

Topical lithium

Topical lithium salts are effective in the treatment of seborrhoeicdermatitis. It is believed to work by reducing the release of fatty acids in the skin. As fatty acids are important for growth in fungi, this reduces the amount of fungi on the skin.

High local concentration of topical lithium also produces an anti-inflammatory effect, by reducing the production of prostaglandins and other eicosanoids. This allows it to be used to treat other inflammatory skin diseases.

Topical lithium is generally well tolerated and does not raise serum lithium levels significantly. It can cause a transient mild skin irritation.